The crystalline lens of the human eye is located in the posterior chamber between the posterior iris surface and the vitreous body It is a biconvex transparent tissue without nerves and blood vessels, weighing approximately 0.2 g. The lens is enveloped in a capsule, a structureless, transparent and elastic membrane bag. Approximately 80 zonular fibers, extending between the capsule and the ciliary body, suspend the lens. The inside of the lens capsule consists of lens epithelial cells and lens fibers. The lens epithelial cells form a monolayer underlying the capsule from the anterior pole to the equator of the lens. These cells continue to undergo cell mitosis throughout life in the area located between the anterior pole and the lens equator The lens epithelial cells that underwent cell mitosis gradually move toward the lens equator and differentiate into lens fibers. These cells make up the rest of the lens. New layers of fiber cells are constantly formed on top of those previously formed The older fiber cells become denser and during the 3rd decade of life a hard nucleus is formed in the middle of the human lens, consisting of old dehydrated fiber cells.
A cataract is defined as every form of opacity in the lens or its capsule; the lens becomes cloudy, resulting in a loss of visual ability A cataract is a painless phenomenon, but decreases the quality of life if the lens is not surgically extracted and replaced by an artificial lens.
When the lens is surgically extracted, an incision is made in the anterior part of the eye, i.e., the cornea or the sclera Then, a viscoelastic material is usually introduced into the anterior chamber to maintain the anterior chamber depth during surgery. An opening is made in the lens capsule by a procedure called capsulorhexis.
Following capsulorhexis, the lens is removed according to one of two principles: extracapsular cataract extraction (ECCE)—the cataractous lens is squeezed out through an opening in the anterior lens capsule and then removed through a 10-12 mm corneal incision, or phacoemulsification—the cataractous lens is dissolved with a special instrument, phaco-probe, by high frequency sonification and rinsed out through a 3-4 mm corneal incision.
Remaining parts of the lens, i.e. lens fibers and lens epithelial cells, are then removed using an irrigation and aspiration device After complete removal of the lens, the lens capsule is filled with a viscoelastic material and an artificial lens is implanted into it. Alternatively, a lens can be molded inside the lens capsule, as disclosed in PCT/EP99/07780. Thereby a cross-linkable polymer is injected into a lens capsule, and the lens is formed in situ. Another method for the same purpose but employing other materials is disclosed in PCT/EP01/04010.
Dyeing of the anterior lens capsule has been used to facilitate capsulorhexis in advanced/white cataract, to enhance critical steps during phacoemulsification and to perform capsulorhexis of the posterior lens capsule. Earlier studies have evaluated dyes, such as crystal violet, fluorescein, and indocyanine green, for dyeing the anterior lens capsule. Some dyes are applied by injection under the anterior surface of the capsule. Others are applied by a certain technique in which the anterior chamber is filled by gas, and the dye is applied on top of the anterior surface of the capsule. After a while, the dye is washed away by irrigation/aspiration and the anterior chamber is filled by a viscoelastic solution followed by capsulorhexis.
After cataract surgery, the most common postoperative complication is posterior capsule opacification (PCO) which has the clinical and economic significance to be considered as an important public health problem. Studies report that the incidence of PCO is ranging from 20% to 40% after approximately 4 years after surgery Migration and proliferation of remaining lens epithelial cells is the main cause of PCO. These cells grow from the peripheral parts of the capsule onto the posterior capsule and continue toward the axial region. Impaired visual acuity is the result caused by cell migration, proliferation and aggregation, the production of extracellular matrix, fibrosis and wrinkling of the lens capsule.
In the current clinical standard, patients who develop PCO are treated symptomatically by YAG laser capsulotomy. In this procedure a YAG laser disrupts the opacified lens capsule and the visual axis is cleared. However, YAG laser capsulotomy exposes patients to the risk of complications that can lead to severe visual impairment or loss of vision, such as retinal detachment, pupillary block glaucoma and cystoid macular edema Other complications associated with YAG laser capsulotomy include damage to implanted intraocular lenses resulting in glare and photophobia, dislocation of intraocular lenses, iritis, vitritis, corneal edema, iris damage and rupture of the anterior hyaloid.
From an economic point of view, symptomatic treatment of PCO is ranked one of the highest of the medical costs in the U.S.A. Thus, development of a procedure to prevent PCO reduces the medical costs related to YAG laser capsulotomy, including the costs for the treatment, its complications, and YAG laser equipment. Accordingly, there is a great need for PCO prophylaxis.
Mechanical and pharmaceutical methods for PCO prophylaxis by removing or destroying residual lens epithelial cells have been developed. However, none of them has been proved to be practical, effective, and safe enough for routine clinical practice.
Capsular polishing, aspiration of residual lens epithelial cells, ultrasound combined with aspiration, cryocoagulation, and osmolysis are examples of methods that have been developed and shown to remove or destroy remaining lens epithelial cells, but none of these methods have been proven to be efficient in PCO prophylaxis.
The design of the artificial intraocular lenses (IOL), such as the shape, size and materials of the IOL implanted during cataract surgery has also been shown to affect the development of PCO. It has been shown that a sharp bend in the capsule, created by a capsule tension ring or an IOL with sharp optic edges, may induce contact inhibition of lens epithelial cell migration on the capsule.
Various anti-metabolites such as doxorubicin, methotrexate, mitomycin, daunomycin/daunorubicin, 5-fluorouracil, colchicines and taxol are effective in inhibiting lens epithelial cells proliferation in vitro. However, in vivo animal studies have shown that there are toxic side effects in the tissues of the eye when anti-metabolites are used in sufficiently high concentration to inhibit lens epithelial cells proliferation. In attempts to avoid side effects on other ocular tissues an immunotoxin specifically inhibiting proliferation of lens epithelial cells has been evaluated. The anti-lens epithelial cell monoclonal antibody binds specifically to lens epithelial cells and carries ricin or saporin that kill proliferating cells. In the experimental studies, antibodies against human antitransferrin and FGF have been used as antibodies against lens epithelial cells. However, no conclusive results have been obtained Another pharmacological approach is to separate lens epithelial cells from the lens capsule. Ethylenediamine tetraacetic acid (EDTA) was included in an irrigation solution and a simulated extracapsular cataract extraction was performed to separate lens epithelial cells. In other attempts, EDTA was used with a viscoelastic material (U.S. Pat. No. 5,204,331 to Nishi et al., 1993), or simply introduced into the lens capsule. When an EDTA solution was included in an irrigation solution and a simulated extracapsular cataract extraction was performed in cadaver eyes, the anterior lens epithelial cells could be separated. EDTA seems not to be more efficient than other agents evaluated in PCO prophylaxis.
Enzymes such as trypsin and DISPOSE (protease) have also been evaluated for separation of lens epithelial cells. When a 2% trypsin solution was included in an irrigation solution and a simulated extracapsular cataract extraction was performed in cadaver eyes, lens epithelial cells were stripped in places. The cell separation was partially successful. However, the zonules were damaged by the trypsin solution. The use of an active enzyme can be a problem even when an enzyme solution is introduced into the lens capsule because it can damage the zonules bound to the lens capsule.
According to U.S. Pat. No. 4,909,784 to Dubroff 1990, when a cell-killing substance is introduced into the lens capsule through a small hole, without first removing the lens, lens epithelial cells are killed. A drawback when using this method is that the efficacy of the treatment may be strongly limited, if the natural lens is not removed before administrating the cell-killing substance. The natural lens may absorb or decrease the efficacy of the substance due to the huge number of lens epithelial cells within the lens. A viscoelastic material that is introduced into the anterior chamber prevents the active agent from escaping from the lens capsule, and prevents damage to the corneal endothelium. In related patents (U.S. Pat. No. 4,909,784 to Dubroff 1990, U.S. Pat. No. 5,013,295 to Dubroff 1991), a syringe to remove the introduced substance from the lens capsule through a small hole was disclosed. However, physically and technically, it seems to be difficult to efficiently remove the substance introduced into the lens capsule before capsulorhexis without damaging the lens capsule. The remaining substance may escape from the lens capsule and damage the cells and tissues facing the anterior chamber during and after capsulorhexis.
An important problem in connection with all methods relating to cataract surgery is the difficulty of observing the interior of the lens capsule, especially behind the iris, in order to ascertain that measure taken were successful, such as the removal of residual lens epithelial cells.
U.S. Pat. No. 5,651,783 (Reynard 1995) discloses a fiber optic sleeve that permits endoscope visualization of intraocular structures either through the surgical handpiece or through an end piece attachment. However, this patent is silent in regard of evaluating the capsular inside in a turbulent flow of irrigation solution and lens materials flowing around the end of the fiber optic during the process of phacoemulsification and irrigation-aspiration, and such evaluation appears very difficult given the premises in the patent. Gwon et al, in J. Refract. Surgery, Vol. 19, November 1993, pp 735-746 discloses that the lens capsule was expanded with air and perfluoropropane by closing a capsulotomy of a size 2.5 to 3.5 mm with a patch, attached to the capsule by Healon and overlapping the capsule by at least 1 mm. The reason was to study the effect on lens regeneration in rabbits and cats Nothing was explained of using the technique in other aspects. Additionally, it seems difficult to use the technique of closing off the capsule with a patch for performing different procedures within the capsule, as the patch would block introduction of devices into the capsule and performance of different methods within the capsule. Furthermore, the authors describe the situation that the capsule is not completely filled by air, but a mixture of air and viscoelastic solution (Healon®).